Comparative Genomic Hybridization as a diagnostic tool for constitutional chromosome abnormalities.

Comparative Genomic Hybridization (CGH) is an established method for detection of genomic imbalance. CGH has been introduced into this laboratory as a tool in the characterisation of constitutional chromosome abnormalities. Following DNA extraction, labelling and hybridization of test and control DNA onto normal human metaphases, regions of genomic imbalance were detected using a fluorescence microscope, CCD image analysis system and dedicated software. We have used CGH in six cases where partial chromosome duplication was identified by G-banded chromosome analysis and fluorescence in situ hybridization (FISH), but where the breakpoints could not be definitively assigned due to ambiguous banding patterns. CGH analysis was informative for these six cases and showed: dup(1)(q31q32.1); dup(4)(q28.2q33); dup(11)(q23.2q25); dup(16)(q21q24); dup(X)(q26.1q28); dup(6)(q23.3q24.3). In two further cases, CGH was uninformative: one case of a small amount of additional material on the short arm of chromosome 8, and one case of del(11)(q14.3q21), dup(10)(q26.11q26.13). It is concluded that these imbalances were beyond the sensitivity of CGH. In another case, a tissue sample from a fetus with raised nuchal translucency failed to grow in culture. Quantitative Fluorescence PCR (QF-PCR) analysis was consistent with a monosomy X (Turner syndrome) karyotype, but interphase FISH with an X chromosome centromeric probe showed two signals. CGH analysis of fetal DNA indicated the presence of only a single X chromosome. A small pericentromeric X marker chromosome may have been the cause of the second FISH signal. We conclude that CGH is a useful diagnostic tool in the elucidation of constitutional chromosome abnormalities. [ABSTRACT FROM AUTHOR]